Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide)
Synaptogenic Peptide · Cognitive
Overview
Dihexa is a synthetic oligopeptide derived from angiotensin IV that potently cognitive function by promoting synaptogenesis. It is 10 million times more potent than BDNF at promoting synapse formation through HGF/c-Met receptor activation.
Binds to hepatocyte growth factor (HGF) with high affinity (Kd = 65 pM) and potentiates its activity at c-Met receptor, activating PI3K/AKT pathways and promoting new synaptic connections with extraordinary potency.
Improvements in spatial, working, and consolidation demonstrated across animal models.
acquisition through increased synaptic plasticity.
Restoration in impairment models including scopolamine-induced amnesia.
Mechanism
Dihexa is a synthetic oligopeptide derived from angiotensin IV that potently cognitive function by promoting synaptogenesis. It is 10 million times more potent than BDNF at promoting synapse formation through HGF/c-Met receptor activation.
Binds to hepatocyte growth factor (HGF) with high affinity (Kd = 65 pM) and potentiates its activity at c-Met receptor, activating PI3K/AKT pathways and promoting new synaptic connections with extraordinary potency.
Improvements in spatial, working, and consolidation demonstrated across animal models.
Research areas
- Dihexa is a synthetic oligopeptide derived from angiotensin IV that potently cognitive function by promoting synaptogenesis. It is 10 million times more potent than BDNF at promoting synapse formation through HGF/c-Met receptor activation.
- Binds to hepatocyte growth factor (HGF) with high affinity (Kd = 65 pM) and potentiates its activity at c-Met receptor, activating PI3K/AKT pathways and promoting new synaptic connections with extraordinary potency.
- Improvements in spatial, working, and consolidation demonstrated across animal models.
- acquisition through increased synaptic plasticity.
- Restoration in impairment models including scopolamine-induced amnesia.
Research notes
- Headaches (most frequent side effect)
- Anxiety or overstimulation
- Sleep disruption when dosed late in day
- Severe or persistent headaches
- Increasing anxiety or panic attacks
References
- pubmed.ncbi.nlm.nih.gov/25187433/
- pubmed.ncbi.nlm.nih.gov/25455861/
- pubmed.ncbi.nlm.nih.gov/34827486/
- pubmed.ncbi.nlm.nih.gov/23055539/
Questions
How much more potent is Dihexa than BDNF for synapse formation?
Dihexa is approximately 10 million times more potent than BDNF at promoting synaptogenesis. This extraordinary potency comes from its picomolar binding affinity for HGF (Kd = 65 pM) and activation of c-Met receptor, enabling profound cognitive effects at very low doses compared to other peptides.
What's the difference between Dihexa and its prodrug Fosgonimeton?
Fosgonimeton is a prodrug form of Dihexa designed for better pharmacokinetics and clinical development. It showed efficacy in Phase I trials for Alzheimer's disease with normalization of P300 latency. Fosgonimeton may be more stable and bioavailable than raw Dihexa, though research is ongoing.
Is Dihexa safe to combine with other cognitive-enhancing peptides?
Combining Dihexa with other potent nootropics like Semax or Selank may cause overstimulation or excessive neuroplasticity. Limited human data exists for combinations. If stacking, start conservatively and monitor for increased headaches, anxiety, or mood disturbances indicating neural overstimulation.